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| Status |
Public on Mar 27, 2019 |
| Title |
Single Cell RNA Sequencing Identifies TGFβ as a Key Regenerative Cue following LPS-induced Lung Injury |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Many lung diseases result from a failure of efficient regeneration of damaged alveolar epithelial cells (AECs) after lung injury. During regeneration, AEC2s proliferate to replace lost cells, after which proliferation halts and some AEC2s transdifferentiate into AEC1s to restore normal alveolar structure and function. Although the mechanisms underlying AEC2 proliferation have been studied, the mechanisms responsible for halting proliferation and inducing transdifferentiation are poorly understood. To identify candidate signaling pathways responsible for halting proliferation and inducing transdifferentiation, we performed single cell RNA sequencing on AEC2s during regeneration in a murine model of lung injury induced by intratracheal LPS. Unsupervised clustering revealed distinct subpopulations of regenerating AEC2s: proliferating, cell cycle arrest, and transdifferentiating. Gene expression analysis of these transitional subpopulations revealed that TGFβ signaling was highly upregulated in the cell cycle arrest subpopulation and relatively downregulated in transdifferentiating cells. In cultured AEC2s, TGFβ was necessary for cell cycle arrest but impeded transdifferentiation. We conclude that during regeneration after LPS-induced lung injury, TGFβ is a critical signal halting AEC2 proliferation but must be inactivated to allow transdifferentiation. This study provides insight into the molecular mechanisms regulating alveolar regeneration and the pathogenesis of diseases resulting from a failure of regeneration.
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| Overall design |
Single cell RNA-Seq analysis of naïve and LPS-injured adult murine lung
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| Contributor(s) |
Riemondy KA, Hesselberth JR, Zemans R |
| Citation(s) |
30913038 |
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| Submission date |
Apr 12, 2018 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Kent Augustus Riemondy |
| Organization name |
University of Colorado School of Medicine
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| Department |
Biochemistry and Molecular Genetics
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| Street address |
12801 E 17th Ave
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| City |
Aurora |
| State/province |
Colorado |
| ZIP/Postal code |
80045 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (10)
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| GSM3094778 |
Expt. 1 Control Mouse, Non Type II lung epithelial cells, technical rep. 1 |
| GSM3094779 |
Expt. 1 Control Mouse, Non-Type II lung epithelial cells, technical rep. 2 |
| GSM3094780 |
Expt. 1 Control Mouse, Type II Alveolar cells |
| GSM3094781 |
Expt. 1 Injured Mouse (LPS), Type II Alveolar cells, technical rep. 2 |
| GSM3094782 |
Expt. 1 Injured Mouse (LPS), Type II Alveolar cells, technical rep. 1 |
| GSM3094783 |
Expt. 2 Control Mouse, Non-Type II Lung epithelial cells, technical rep. 1 |
| GSM3094784 |
Expt. 2 Control Mouse, Non-Type II Lung Epithelial cells, technical rep. 2 |
| GSM3094785 |
Expt. 2 Control Mouse, Type II Alveolar cells |
| GSM3094786 |
Expt. 2 Injured Mouse (LPS), Type II Alveolar cells, technical rep. 1 |
| GSM3094787 |
Expt. 2 Injured Mouse (LPS), Type II Alveolar cells, technical rep. 2 |
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| Relations |
| BioProject |
PRJNA449866 |
| SRA |
SRP139766 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE113049_cell_metadata.tsv.gz |
414.9 Kb |
(ftp)(http) |
TSV |
| GSE113049_count_matrix.tsv.gz |
21.5 Mb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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